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SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST DEGREE RELATIVES * AJAI KUMAR, G. L. UPADHY,lI.YA AND J. K. TRIVEDI** Department of Biochemistry. S. N. Medical College. Agra - 282 002 ( Received on November 12. 1983 ) Sammary : Blood samples of 20 schizophrenic patients. 20 of their first degree relatives and 43 nOrmal subjects, both male and female. were taken and serum CPK estimation was done by using calorimetric sigma procedure. The schizophrenics and their 1st degree relatives had shown a significantly higher mean±S.D. CPK levels of 31.25±21.6 and 16.15±4.7 Sigma Units respectively as compared to 11.16±3.38 Sigma Units in nOrmals (Cal. t=573. tab. t=1.65 at df=61 and P<05) A significant difference between the CPK levels of male and female of the three groups was found (P<.05). The males of normal. Schizophrenics and 1st degree relatives had significantly higher mean±SD CPK levels of 12.65±3.05, 47.4±18.73 and 19.5±1.93 Sigma Units respectively as compared to levels of 9.45±2.94. 15.10±4.33 and 12.71 ±2.47 sigma units in fE'males of the corresponding three groups (P<.05). Males of the patlE:nts and 1st degree relatives had shcwn higher levels than the female:s. A highly significant and positive correlation was found between the mean serum CPK levels of Schizophrenic patients and their 1st degree relatives (CorrE·lation cOeffiCient (Yy)=0.79). Key words : serum CPK INTRODUCTION SChizophreniCS Mean serum CPK levels were found to be elevated during acute psychiatric episodes by Meltzer (5.6) and by other workers (1, 12. 13). Recently (2. 16) isoenzymes of CPK in serum and CSF of schizophrenics ar.d in acute psychotic states have been investigated. CPK isoenzymes have been found to increase in other conditions like brain damage and heart damage, alcoholism and muscular diseases (15). Several investi- gators have suggested that motor activity was the main reason for increased CPK levels during acute psychotic episodes According to MeltZEr (7. 8) the increased motor activity is one of the main contributing factor for the raised level, but observed that the CPK levels in functional psychotic patients are still higher even after the motor activity was controlled. Serum CPK activity has been tested in patients with progressive muscular dystrophy and their relatives for the detection of genetic carriers (4). 'Abstract published at thE; IXth Annual Conference of the Association of Clinical Biochemists of India. held at P.G.I.M.E. and Research. Calcutta. nn Dec. 19-21. 1982. "Present address: Lecturer In Psychiatry. K.C;.'s Medical COllege. Lucknow - 226 003

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Page 1: SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST

SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST DEGREERELATIVES*

AJAI KUMAR, G. L. UPADHY,lI.YA AND J. K. TRIVEDI**

Department of Biochemistry.S. N. Medical College. Agra - 282 002

( Received on November 12. 1983 )

Sammary : Blood samples of 20 schizophrenic patients. 20 of their first degree relatives and 43 nOrmal

subjects, both male and female. were taken and serum CPK estimation was done by using calorimetric

sigma procedure. The schizophrenics and their 1st degree relatives had shown a significantly higher

mean±S.D. CPK levels of 31.25±21.6 and 16.15±4.7 Sigma Units respectively as compared to

11.16±3.38 Sigma Units in nOrmals (Cal. t=573. tab. t=1.65 at df=61 and P<05) A significant

difference between the CPK levels of male and female of the three groups was found (P<.05). The

males of normal. Schizophrenics and 1st degree relatives had significantly higher mean±SD CPK

levels of 12.65±3.05, 47.4±18.73 and 19.5±1.93 Sigma Units respectively as compared to levels

of 9.45±2.94. 15.10±4.33 and 12.71 ±2.47 sigma units in fE'males of the corresponding three groups

(P<.05). Males of the patlE:nts and 1st degree relatives had shcwn higher levels than the female:s.

A highly significant and positive correlation was found between the mean serum CPK levels of

Schizophrenic patients and their 1st degree relatives (CorrE·lation cOeffiCient (Yy)=0.79).

Key words : serum CPK

INTRODUCTION

SChizophreniCS

Mean serum CPK levels were found to be elevated during acute psychiatric episodes

by Meltzer (5.6) and by other workers (1, 12. 13). Recently (2. 16) tr~e isoenzymesof CPK in serum and CSF of schizophrenics ar.d in acute psychotic states have beeninvestigated. CPK isoenzymes have been found to increase in other conditions like braindamage and heart damage, alcoholism and muscular diseases (15). Several investi­gators have suggested that motor activity was the main reason for increased CPK levelsduring acute psychotic episodes According to MeltZEr (7. 8) the increased motor activityis one of the main contributing factor for the raised level, but observed that the CPKlevels in functional psychotic patients are still higher even after the motor activity was

controlled. Serum CPK activity has been tested in patients with progressive musculardystrophy and their relatives for the detection of genetic carriers (4).

'Abstract published at thE; IXth Annual Conference of the Association of Clinical Biochemists of India. heldat P.G.I.M.E. and Research. Calcutta. nn Dec. 19-21. 1982.

"Present address: Lecturer In Psychiatry. K.C;.'s Medical COllege. Lucknow - 226 003

Page 2: SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST

Volume 28Number 2

Serum CPK in Schizophrenics and their RelJt;ves 129

We have investigated serum CPK levels in relation to male and female of schizo­phrenic patients in acute phase of illness and their 1st cegree relatives and these resultsare given below.

MATERIAL AND METHOD

Patients diagnosed as schizophrenic in acute phase of illness and their first degreerelatives have been studied. Serum CPK !evels were determined by Sigma method videSigma Technical Bulletin No. 520(10). Patients ar,d their first degree relatives wereinterviewed for other factors that might influence the CPK levels Only those patientsand relatives. who had not received t'le intramuscular injection suffered the seizuredisorder/brain trauma or other brain damage were included in the present work. Historyof muscle damage or heart ailment was also taken into consideration and only thosesubjects who wel'e sound in health and mind and devoid of above disorders were includedin the present study in order to know the normal level of serum CPK.

Assay: Colorimetric sigma method of serum CPK estimation was carried outwithin an hour of the blood collection in schizophrenic ~atients. their 1st degree relatives

and no mal subjects. The method was slightly modified where one mg reduced gluta­thione. found to be optimum for enzyme activity. was added in incubation mixture beforeADP. The solutions of phosphocreatine. reduced glutathione and ADP were kept frozenat -10°C when these are not used.

Tre assay system adopted was as follows: substrate 0.5 mi. 1.5 mg creatinephosphate in 0.1 M Tris buffer pH 7.5 containing 1.5 mg MgCIz. 6H zO then added 0.1mi. 1.0 mg reduced glutathione. pH 7.0 and 10 fll serum in the test only and was prein­cubated for 2 or 3 min at 3rC. The reaction was started by the addition of 0.1 mi.0.82 mg ADP. pH 7.0. After 30 min of incubation at 3rC the reaction was terminatedby the addition of 0.2 mi. 3.6 mg p-OH mercuric benzoate. then added 10 fll serum inthe control. In order. 1.0 mi. 20 mg Q:-naphthol (prepared in stock al kal i - 6 g NaO Hand 12.8 g Na2 CO)/100 ml distilled water). 1.0 mi. 0.05% freshly prepared diacetyland 7.0 ml distilled water, was added and content of centrifuge tubes were mixed thorou­ghly. Tubes were incubated for 15 min at 3rC for final color development then centri­fuged for 5 min at 2.000 g. Pink colour developed is directly proportional to the CPKactivity. Readings of Test control and standard was taken at 530 r.m (green filter) in acolorimeter by setting inst(ument at zero O. D. with the blank.

One Sigma unit is defined as that amount of enzyme which will liberate 1 milli

micromole creatine per minute at 3JOC from phosphocreatine per ml of Serum.

Page 3: SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST

130 />.ial Kumar er at.

RESULTS

Awil-June 1984Ind. J. Physiol. Pharmac.

As can be seen in Table I the schizephrenic patients and their 1st degree relativeshad shown a significantly higher mean±SD CPK levels of 31.25±21.6 and 16.15±4.7Sigma units (respectively as compared to 11.16±3.38 units in normals (Cal. t=5.73.

tab. t=1.65 at df=61 and P<.05).

TABLE I : Serum CPK levels in different categories of either sex.

There was a significant difference between the CPK levels of male and femaleof the three groups (P<.05). The males of normal. schizophrenics and their first degreerelatives had significantly higher mean±S.D. CPK levels of 12.65±3.05. 47.4±18.73and 19.5±1.93 Sigma units respectively as compared to levels of 9.45±2.94. 15.1'O±4.33 and 12.71 ±2.47 Sigma units in females of the corresponding three groups. Althoughsignificant increase (P<.05) In serum CPK level was observed for both male and femaleschizophrenic and their 1st deQree relatives. the increase in case of female was less incomparison to males of the two groups and almost four fold increase was obtained formale schizophrenic patients.

The mean serum CPK levels in schizophrenic patients and their 1st degree relativeswere statistically found to be highly significant and positively correlated (correlatlon­coefficient (Yyx) =0.79).

DISCUSSION

Our findings are in agreement to the earlier reports that schizophrenic patientsin acute phase of iilness have higher mean serum CPK levels than those of the normalsubjects. The increase in CPK level was found for both male and female of the patients

Page 4: SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST

Volume 28Number 2

Serum CPK in Schizophrenics and their Rel~tives 131

and their relatives. But males had shown significantly higher (P<.05) level,s than thefemales of all the three categories. And almost four fold increase in the CPK level wasobserved for male schizophrenics. It is reported that normal male showed higher CPKlevels than the females (9) and enzyme activity is influenced by musculature and muscleactivity in the subject (3). In light of the reports (3. 9) it is possible that male patientsmay have more increase in serum CPK than the females. The same trend of sharp risein CPK level of male 1st degree relatives of the patients was also observed. It may be

possible that factors responsible for elevation of serum CPK are more aggrevated in malesthan the females. The artifacts in the technique of estimation seems to be quite un­likely. Recently (14), serum and CSF enzymes have been estimated in acute psychoticsand contrary to the reports of Meltzer they have not found significant increase in mean

serum CPK levels. In our findings the male patients in acute phase of illness had showna substantial increase in CPK levels. Whereas only 60% female petients had a slightbut significant increase in enzyme ,evel. It is of interest for future investigations in iCPKlevel of male and female schizophrenics.

First degree relatives of the patients have shown the tendency to have raised

levels of the serum CPK than the normal subjects. It seems that possibly some commonfactor exist which tend to raise the levels in the schizophrenics and their relatives. Itcan be of significance for the hereditory role in schizophrenic illness.

Several factors have been attributed for the increase in CPK levels in acute psychoticpatients and brain dysfunctions. It is believed that due to cell membrane permeability.increased efflux of enzyme from the skeletal muscle occurred and was possible causefor raised CPK levels (5 to 8). Schizophrenics have been shown to possess the genera­lised increase in metabolic activity (11). These factors may be regarded as possibleexplanation for, raised CPK levels in schizophrenia.

ACKNOWLEDGEMENTS

The authors thank Mr. Diwaker Sinha. Statistician-cum-Lecturer. M.L.N. MedicalCollege, Allahabad, for the kind help rendered by him in the statistical work withoutwhose co-operation it would have been impossible to complete this study.

REFERENCES

1. Colfey, J.W.• A.F. Guschwan and P.G. Heeth. Serum creatinine kinase. a!dolase, and copper in acute andchroniC schizophrenics. BioI. Psychiatry. 2 : 331-339. 1972.

2. Fairbunn. C G.•A.E.H. emery and D. Burt. The isozymes of CPK in acute psychotic states. Brit. J. Psychiatry.138 : 81-82. Jan. 1981.

Page 5: SERm,,! CPK LEVELS IN SCHIZOPHRENICS AND THEIR FIRST

132 Ajai Kumar et al. April-June 1984Ind. J. Physiol. Pharmac.

3. Kontinen. A. Muscular activity and serum CPK. Cardiology, 43 : 58. 1963.

4. Laszlo. A. and L. Salgo. Trst of serum CPK activity in patients with progressive muscular dystrophy and theirrelatives for the detection of genetic carriers. Crv. Hetil. 122 : (24) : 1453-1456.1981.

5. Meltzer. H.Y. Serum CPK in schizophrenia. Am. J. Psychiatry, 133 : (2) : 192-197. 1976.6. Moltzer. H.Y.• JR. Stanton and S. Schlessinger. Mean Serum CPK activity in patients with functional psychosio.

Arch. Gen. Pshchiatry. 37 (6) : 650-655. 1980.

7. Meltzer. H.Y. Neuromuscular abnormalities In the major mental illness. I: Serum enzyme studies. in biologyof the major psychosis: A comparative Analysis. Edited by Freeman. D.S .• New York. Raven Press. 1975.

8. Meltzer. H.Y. Neuromuscular dysfunction in schizophrenia. Schizcphre Bu!l... 2 : 106-135.1976.

9. Rosalki. S.B. Normal values of serum CPK levels. J. Lab. C/in. Med.• 69 : 696. 1967.

10. COlorimetric determination of CPK in serum Or plasma at 500-540 nm. Sigma Techmcal Bulletin. No. 520.11. Slater. E. and M. Roth. Schizophrenia. Clmical Psychiatry 3rd ed.12. Soni. S.D. Serum CPK in acute psychosis. Brit. J. Psychiatry. 128 : 181-183.1976.

13. Schubert. D.S .• K. Brocco. F.T. Miller and M. Patterson. Serum CPK levels in patients meeting the St. LouiseResearch diagnostic criteria for schizophrenic. Am. J. Psychiatry. 139 (4) : 491-493. 1982.

14. Subhash. M.N .• S.M. Channabasavanna. S. Bhat. and B.S. Sridhara Rama Rao. Serum and cerebrospina Ifluid enzymes in acute Psychotics. Ind. J. Psychol. Medicine. 34-37. 1982.

15. Tsung. S.H. Several conditions causing elevation of serum CPK·MB and CK-BB. Am. J. C/in. Pathol.. 75(5) : 711-715. 1981.

16. Zweig. M.H .. A.C. Vansteirleghem and E.F. Torrey. CPK isozymes in the serum and CSF of schi?ophrenicpatients. Arch. Gen. P~ychlat·y. 38 (10) : 1107-1109.1981.